P1598: UTILITY OF ‘OPEN/CLOSED’ ADAMTS13 IN MONITORING IMMUNE TTP
Authors: Nithya Prasannan, Bertina Dragunaite, Rens de Groot, Deepak Singh, Karen Vanhoorelbeke, Marie Scully
Journal: HemaSphere (2023)

Topic: 32. Platelet disorders Background: Open ADAMTS13 conformation is a hallmark of acute immune mediated TTP (iTTP) and a novel biomarker of subclinical iTTP in remission. Aims: We investigated ADAMTS13 conformation in iTTP at diagnosis and remission, focusing on ADAMTS13 level at which a closed conformation is likely. Conformation in elective rituximab (ER) patients and as a predictor of requirement for elective treatment were also investigated. Methods: Conformation index (CI) determined using 1C4-ELISA at diagnosis (n=98), remission (ADAMTS13 activity>50%, includes repeat sampling with increasing ADAMTS13 activity over time in some patients, n=144), and elective rituximab (ER, n=61) patients. Post-ER samples had ADAMTS13 activity>50% measured 3 months post-ER/peak ADAMTS13 activity. Peak ADAMTS13 activity was defined as highest ADAMTS13 activity achieved within 1 year of diagnosis prior to any ADAMTS13 activity decline, or >1 year from diagnosis if no further treatment required. ADAMTS13 antigen (Ag) and anti-ADAMTS13 IgG antibody (Ab) levels were determined using ELISA. Median ADAMTS13 activity, Ag and Ab levels are expressed as % (±range). Results: 97/98 (99%) acute iTTP patients had an open ADAMTS13 conformation at diagnosis, median ADAMTS13 Ag 11.8% and Ab 36.9%. 1/98 had closed conformation at diagnosis with ADAMTS13 activity<10%, ADAMTS13 Ag 86.4% and Ab 19%. 75/144 (52%) remission samples had open conformation with median ADAMTS13 activity 69%, Ag 86.8% and Ab 4%. Of the 75 with open conformation in remission, 24 (32%) had positive Ab (11.1% (6.6-64%)) and 46 (61%) had open conformation with no demonstratable Ab. 69/144 (48%) had closed conformation, with higher median ADAMTS13 activity 102% (p<0.0001) and Ag 124.1% (p<0.0001). Ab was lower (median 2.5% (p<0.0001)). 4 additional patients did not achieve ADAMTS13 activity>50% and therefore conformation was not tested in remission. Higher ADAMTS13 activity was associated with lower CI (n=242, includes diagnostic and remission samples, p<0.0001). 54% (81/150) had open conformation despite ADAMTS13 activity>50%, prompting analysis of ADAMTS13 conformation at peak ADAMTS13 levels. At peak ADAMTS13 activity, 24% (14/59) had open conformation with normal but significantly lower ADAMTS13 activities compared to those in closed conformation (89.3% vs 109.4%, p=0.02). ADAMTS13 Ag (113.8% vs 124%, p=0.39) and Ab (4% vs 3%, p=0.17) levels showed no difference. 58 pre-ER samples had open conformation, median ADAMTS13 activity 11.4%, Ag 34.3%, Ab 5.1%. Remission samples were analysed according to peak and non-peak ADAMTS13 activity post-ER; 35/47 (76%) of those with peak activity had closed conformation compared to 3/14 (21%) at 3 months with non-peak levels, p=0.0004. 23% patients with open conformation required ER at median 17 months (6-79 months). 25% patients with closed conformation required ER at median 28 months (9-104 months, p=0.7). 73% and 67% did not need further treatment regardless of open or closed conformation respectively (p=0.3). Summary/Conclusion: Patients with closed conformation in remission had a significantly higher ADAMTS13 and ADAMTS13 Ag, with normal but lower median IgG Ab than patients with open conformation. Peak ADAMTS13 activity was more likely to predict closed conformation than Ag or Ab levels. Over 50% with open conformation had no demonstratable Ab suggesting subclinical disease which is not evident through ADAMTS13 testing alone. Closed conformation was also more likely with peak post-ER ADAMTS13 activities. Similar proportion of patients required ER despite conformation, with some suggestion that this is more delayed in patients with closed conformation but was not statistically significant. Keywords: TTP